Jaundice BY Dr KARAN KUMAR

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JAUNDICE

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  • bilirubin comes from breakdown of haem by the RES (splenic, hepatic and marrow macrophages) 80% from RBC breakdown and 20% from other haem containing proteins. Within macrophages oxidised to biliverdin and then reduced to uncongulatedbilirubin which is released into plasma and is water insoluble, transported bound to plasma proteins (albumin). This is then actively transported into hepatocytes, where it is conjugated mostly to glucoronic acid (by glucuronyltransferase congenital failure of which is Gilbert’s disease) and becomes water-soluble conjugated bilirubin which is concentrated and actively excreted into the bile canaliculi (failure of this is Dubin Johnson type hyperbilirubinaemia). Bilirubin is then secreted along with bile salts and sodium into the intestine (bile), where it is broken down to urobilinogen. 90% of urobilinogen is broken down in the gut to urobilin and stercobilin and excreted in stools, other 10% is re-absorbed. The reabsorbed urobilinogen is either recirculated into bile by liver or excreted in urine.Therefore only conjugated bilirubin can be excreted in urine because it’s water-soluble. Therefore haemolytic jaundice is acholuric.Van den Burgh reaction detects conjugated (direct) or unconjugated (indirect) bilirubinCholecystographic media compete with conjugated bilirubin for concentration and therefore will not be concentrated in the setting of excess bilirubinIn obstructive jaundice the pale stools are due to decreased bile pigments, whereas stools may be darker than usual in haemolytic jaundice due to excess stercobilinogen productionIf liver function is impaired there will be decreased ability to re-excrete urobilinogen and stercobilinogen and more will appear in urineComplete obstruction of biliary tree will lead to absence of urobilinogen from urine – prolonged absence indicates pancreatic head malignancy rather than stones because they will let some bile throughTherefore examination of the stools and testing urine for urobilinogen can help differentiate types of jaundice.Bilirubin functions as an anti-oxidant
  • Usually easy to differentiate pre-hepatic from hepatic and post-hepatic but the latter two may be difficult to differentiate from eachother and are often simultaneously presentIn hepatic jaundice urinary urobilinogen is often raised because of the inability of the liver to re-excrete reabsorbed urobilinogenDirect Coombs’ test detects antibodies coating RBC’s and if positive means likely haemolytic anaemiaIndirect Coombs’ test detects circulating antibodies to RBC’s and is used in pregnency and prior to transfusionRaised INR in post-hepatic is due to decreased fat and therefore vit K absorption from gut, in hepatic it’s from both this and decreased synthesis of prothrombin by damaged liver
  • Jaundice BY Dr KARAN KUMAR

    1. 1. JAUNDICE •YELLOWISH DISCOLOURATION OF SCLERA/TISSUE DUE TO INCREASED LEVEL OF BILIRUBIN IN BODY. Normal level of bilirubin in body<1MG/DL (0.3MG OF WHICH IS CONJUGATED)
    2. 2. D/D OF YELLOW SKIN • CAROTENODERMA • QUINACRINE/PHENOL POISONING • JAUNDICE
    3. 3. PATHOPHYSIOLOGY OF JAUNDICE • INCREASED PRODUCTION OR DECREASED EXCRETION OF BILIRUBIN • BILIRUBIN IS A BYPRODUCT OF METABOLISM OF HEMOPROTEIN LIKE HAEMOGLOBIN,MYOGLOBIN AND CYTOCHROMES • 1g Hb - 34mg bilirubin • IT IS BEING PRODUCED IN RETICULOENDOTHELIAL SYSTEM (LIVER AND SPLEEN)
    4. 4. HAE M HAEM OXYGENASE BILIVERDIN BILIVERDIN REDUCTASE BILIRUBIN
    5. 5. • THIS UNCONJUGATED BILIRUBIN IS BOUND TO ALBUMIN AND TRANSPORTED TO LIVER • IN LIVER,BILIRUBIN IS BOUND TO GLUCOURONIC ACID,MEDIATED BY ENZYME UDPGT • THIS CONJUGATED BILIRUBIN IS WATER SOLUBLE AND RELEASED INTO BILE VIA MDR-2 PROTEIN (RATE LIMITING STEP)
    6. 6. Bilirubin Metabolism
    7. 7. MEASUREMENT OF SERUM BILIRUBIN • VAN DEN BERGH REACTION • IT IMPLIES USAGE OF SULFANILLIC ACID AND ALCOHOL IN CONSECUTIVE STEPS • URINARY BILIRUBIN IS DETECTED BY MEAN OF DIPSTIC TEST-ICOTEST
    8. 8. APPROACH TO A PATIENT OF JAUNDICE • HISTORY (TRAVEL,RESIDENCE,DIETARY,SEXUAL,BLOOD TRANSFUSION OR ANY DRUG USAGE,ALCOHOL CONSUMPTION) • PHYSICAL EXAMINATION (PALPATION OF LIVER,SPLEEN,STIGMAS OF CHRONIC LIVER DISEASE) • LAB INVESTIGATIONS(SGPT,SGOT,ALP, P.T,S.PROTEIN,VIRAL MARKERS) • IMAGING (ULTRASOUND,MRCP,ERCP)
    9. 9. ISOLATED HYPERBILIRUBINEMIA • CAN BE EITHER 1. CONJUGATED HYPERBILIRUBINEMIA(>15%DIRECT BILIRUBIN) OR 2. UNCONJUGATED HYPERBILIRUBINEMIA(<15%DIRECT BILIRUBIN)
    10. 10. UNCONJUGATED HYPERBILIRUBINEMIA 1.CAUSED BY INCREASED PRODUCTION OF BILIRUBIN (HEMOLYTIC ANAEMIA OR INEFFECTIVE ERYTHROPOEISIS) 2.DECREASED UPTAKE OF UNCONJUGATED BILIRUBIN BY HEPATOCYTES ( DRUGS LIKE PROBENECID,RIFAMPICIN,RIBAVIRIN,BREAST MILK JAUNDICE IN NEONATE). 3.DECREASED CONJUGATION OF BILIRUBIN IN HEPATOCYTES(CRIGLER NAJJAR-I &II,GILBERT SYNDROME)
    11. 11. HEMOLYTIC JAUNDICE • SPHEROCYTOSIS,ELLIPTOCYTOSIS,G6PD DEFFICIENCY,THALASSEMIA,HBS,AIHA,PNH • SERUM BILIRUBIN LEVEL RARELY INCREASE TO MORE THAN 5MG/DL • HIGH ASSOSCIATION WITH GALL STONES
    12. 12. CRIGLER NAJJAR SYNDROME • TYPE I: RARE DISEASE,CAUSED BY COMPLETE ABSENCE OF ENZYME BILIRUBIN UDPGT. S.BILIRUBIN>20 MG/DL DEATH OCCUR IN INFANCY.. • TYPE II:MORE COMMON,PARTIAL ABSENCE OF ENZYME BILIRUBIN UDPGT. • S.BILIRUBIN-8 TO 25MG/DL • USUALLY SURVIVE UPTO ADULTHOOD
    13. 13. GILBERT SYNDROME • COMMON CONDITION • MORE IN MALES • ALSO CAUSED BY DECREASED ACTIVITY OF ENZYME BILIRUBIN UDPGT • S.BILIRUBIN RARELY EXCEED TO MORE THAN 6MG/DL • NO HEMOLYSIS
    14. 14. ISOLATED CONJUGATED HYPERBILIRUBINEMIA • DUBIN JOHNSON SYNDROME:MUTATION IN MDR-2 PROTEIN • ROTOR SYNDROME:CAUSED BY DEFECTIVE STORAGE OF BILIRUBIN IN HEPATOCYTES • BOTH ARE BENIGN CONDITIONS,REQUIRE NO TREATMENT
    15. 15. HYPERBILIRUBINEMIA WITH ALTERED L.F.T’S • HEPATOCELLULLAR PATTERN: ELEVATED ALT/AST OUT OF PROPORTION TO ALKALINE PHOSPATASE • CHOLESTATIC PATTERN: ELEVATED ALKALINE PHOSPATASE OUT OF PROPORTION TO AMINO TRANSFERASE
    16. 16. HEPATOCELLULAR JAUNDICE 1. VIRAL HEPATITIS (HAV,HEV,HBV,HCV,..EBV,CMV) 2. ALCOHOLIC LIVER DISEASE 3. DRUG INDUCED(H,R,Z, HALOTHANE,PHENYTOIN,VALPORATE,NSAID, PI’S,NRTI’S) 4. WILSONS DISEASE 5. AUTOIMMUNE HEPATITIS
    17. 17. CHOLESTATIC JAUNDICE • INTRAHEPATIC CHOLESTASIS:(VIRAL HEPATITIS,ALCOHOLIC HEPATITIS,DRUG TOXICITY,PRIMARY BILLIARY CIRRHOSIS,PRIMARY SCLEROSING CHOLANGITIS,VANISHING BILE DUCT SYNDROME, T.P.N, PARANEOPLASTIC SYNDROME, GVH RXN) • EXTRAHEPATIC CHOLESTASIS: (CHOLEDOCHOLITHIASIS,STRICTURE,PERIAMPULLARY TUMOUR,CHRONIC PANCREATITIS)
    18. 18. L.F.T’S AND ITS IMPLICATION IN DIAGNOSIS OF JAUNDICE • S.BILIRUBIN AND ITS FRACTIONS (DELTA BILIRUBIN) • LIVER ENZYMES: 1 A.L.T 2 A.S.T 3 ALP 4 GGT 5 NUCLEOTIDASE’5 • S.PROTEIN • CLOTTING FACTOR • PROTHROMBIN TIME
    19. 19. 1.SERUM BILIRUBIN • HAS 2 COMPONENTS-DIRECT AND INDIRECT • >3MG/DL-RESPONSIBLE FOR YELLOW SCLERA • USED TO DIFFERENTIATE B/W HEPATOCELLULAR AND CHOLESTATIC JAUNDICE • DELTA BILIRUBIN-CONJUGATED BILIRUBIN BOUND TO ALBUMIN
    20. 20. LIVER ENZYMES • A.L.T: SPECIFIC TO LIVER,VALUE INCREASED SIGNIFICANTLY IN HEPATOCELLULAR JAUNDICE. • A.S.T:FOUND IN LIVER,CARDIAC MUSCLE,SKELTAL MUSCLE,KIDNEY, BRAIN,RBC’S &WBC’S • AST/ALT>3:1- INDICATOR OF ALCOHOLIC LIVER DISEASE • ALP,GGT,5’NUCLEOTIDASE-MARKERS OF CHOLESTASIS
    21. 21. S.PROTEIN • DECREASED ALBUMIN IS INDICATOR OF CHRONIC LIVER DISEASE • ELEVATED GLOBULIN IS ALSO SEEN
    22. 22. COAGULATION FACTORS • ALL CLOTTING FACTOR ARE SYNTHESISED IN LIVER(EXCEPT FACTOR VIII) • FACTOR V IS MOST SPECIFIC TO LIVER INJURY
    23. 23. PROTHROMBIN TIME • INCREASED IN CASE OF HEPATOCELLULAR AS WELL AS CHOLESTATIC JAUNDICE. • IF CORRECTED BY GIVING VITAMIN KINDICATES CHOLESTATIC COMPONENT • ALTERED EVEN IN ACUTE LIVER INJURY
    24. 24. Investigations Pre-hepatic Hepatic Post-hepatic Urine No Bilirubin Urobilinogen ? Bilirubin  Urobilinogen Bilirubin Urobilinogen Faeces Dark Pale Pale Blood FBC - Reticulocyte count Coombs’ test Bilirubin (<15% – conjugated) ALP Normal PT Normal Bilirubin – mixed conjugated & unconjugated  ALP, γGT AST, ALT  PT – not correctable with Vit K Bilirubin (>15% conjugated)  ALP, γGT  PT – correctable with Vit K
    25. 25. Management • Symptom relief – Pain, itch • Fluid resuscitation • Correction of coagulopathy • Treat secondary complications – Sepsis, bleeding, anaemia • Treat underlying cause – Medical or surgical
    26. 26. THANK YOU

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